The object of this study is to elucidate mechanisms of differentiation of B-cell precursors by examining features of differentation arrest in pre-B-cell malignancies. The phenotype of 80 leukemias and lymphomas was determined by immunofluorescence techniques. Several FCC lymphomas demonstrated partial differentiation in that they contained large accumulations of intracytoplasmic immunoglobulin. Forty-one lymphomas and leukemias were examined for natural killer (NK) cell phenotype by staining for surface and cytoplasmic antigens detectable by the monoclonal antibody, HNK-1. Very few cells were positively identified, and no lymphomas or leukemias of NK phenotype were found. A leukemic cell line, Mays FI[unreadable]2[unreadable], was established in methyl cellulose culture. The interesting feature of these cells is that they lack surface Ig and light chain expression but contain cytoplasmic gamme chains, suggesting a pre-B switch from mu to gamma. DNA extracts from this and other lines are being analyzed for Ig gene rearrangements, especially for C[unreadable]mu[unreadable] gene deletions, using cDNA probes. IL-1, which has been shown to stimulate pre-B-cell differentiation in mice, was prepared from human monocytes and used to stimulate fresh ALL cells and leukemic cell lines. A single ALL showed no proliferative, but moderate, differentiative response. Studies of the effect of IL-1 and receptors for IL-1 on other human leukemic cells are underway. Additional studies for the coming year include: (1) examination of the membrane and secretory physiochemical properties of pre-B leukemic cell mu and gamma chains; (2) subcloning of leukemic and lymphomatous cells to explore the contribution of cell cycle to differentiation arrest; (3) hybridization of leukemic cells with nonsecretory myeloma cells to determine the effects of fusion on surface Ig and light chain expression; and (4) exploration of growth factor requirements of pre-B and B leukemic cells. (AB)